A 35-year old lady suffers from recurrent attacks of migraine. She experiences severe headaches with associated visual auras 5 days a month. Over-the-counter analgesics were ineffective. Her migraines are more frequent when she has her menses. 

(a) Describe the mechanism of action of non-steroidal anti-inflammatory drugs in acute migraine. (3 marks) 

MOA of NSAIDs is blocking cyclooxygenase (COX), which are enzymes involved in producing prostaglandins which cause pain and inflammation. NSAIDs are widely used for acute migraine treatment in mild to moderate migraine. Their action is mainly to inhibit neurogenic inflammation and the reversal of CNS sensitization associated with migraine.

This MOA is considered to be non-specific with regards to the pathophysiology of migraine (vs triptans which are more specific for migraine pathophysiology).

Need to be aware of side effects:

• GI irritation
• nephrotoxicity
• Anti-platelet effect (mostly aspirin)

Cautions/contraindiations:

• peptic ulcer disease, inflammatory bowel disease, gastric bypass surgery
• aspirin allergy
• renal dysfunction
• concomitant anticoagulants
• medication overuse headache (MOH) - limit use to 14 days a month or fewer.
  

NSAIDs are first-line treatment for mild to moderate migraine.

Paracetamol (acetominophen)can also be used but less effective for migraine.

More serious migraine is treated with triptan.

Aspirin is effective at doses of 1,000 mg but has the greatest risk of gastric irritation.

Ibuprofen (400 mg) is often chosen for its availability and tolerability - fast acting, takes around 2 hours for max effect to take place. Needs to be taken around three times a day. Liquid capsules also available.

Diclofenac is available as a powder or tablet and is as effective as ibuprofen. Powder formulation (diclofenac potassium) has a fast onset of action and short half life.

Naproxen (500 mg) has a slower onset of action but longer half-life. It has also been shown to help in more severe migraine headache.

The combination of paracetamol/aspirin/caffeine has good evidence of effectiveness and can also be used as a first-line treatment for migraine.

There currently are not any studies to show superiority of any NSAID over the other for migraine, the choice of NSAID should be based on availability and adverse effect profile.

https://www.aafp.org/pubs/afp/issues/2018/0215/p243.html

Ong, J.J.Y., De Felice, M. Migraine Treatment: Current Acute Medications and Their Potential Mechanisms of Action. Neurotherapeutics 15, 274–290 (2018).

https://ihs-headache.org/wp-content/uploads/2020/06/Tfelt-Hansen.pdf